Nonsteroidal anti-inflammatory drugs (hereinafter referred as “NSAIDs”) are among the most commonly prescribed drugs. The ability of NSAIDs to treat inflammatory disorders is attributed to their ability to inhibit cyclooxygenase, the enzyme responsible for biosyntheses of the prostaglandins and certain autocoid inhibitors, including inhibitors of lipoxygenase and cyclooxygenase (such as cyclooxygenase-I and cyclooxygenase-II). Aceclofenac belongs to a group of NSAIDs. Chemically, aceclofenac is 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid, carboxymethyl ester of formula I. It is used to relieve pain and inflammation in arthritic conditions. It is also indicated for the treatment of a form of arthritis called as ankylosing spondylitis, inflammatory disease of the joints and osteoarthritis.

Proton pump inhibitors (PPIs) are a class of acid-labile pharmaceutical compounds that block gastric acid secretion pathways. They suppress gastric acid secretion by the inhibition of the H+-K+-ATPase enzyme system at the secretory surface of the gastric parietal cell. Rabeprazole sodium is one such proton pump inhibitor. Rabeprazole sodium, a substituted benzimidazole inhibits gastric acid secretion. Chemically, rabeprazole is 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]-methyl]sulfinyl]-1H-benzimidazole sodium salt of formula II. It is indicated for the treatment of Symptomatic Gastroesophageal Reflux Disease (GERD), pathological hypersecretory conditions, including Zollinger-Ellison Syndrome and maintenance of healing of erosive or ulcerative Gastroesophageal Reflux Disease (GERD).

Paracetamol, also known as acetaminophen, 4′-hydroxyacetanilide, is a non-opiate, non-salicylate analgesic and antipyretic. Chemically, it is N-(4-hydroxyphenyl)ethanamide of Formula II. Acetaminophen provides temporary relief of minor aches and pains with heartburn or acid indigestion and upset stomach associated with these symptoms.

U.S. Pat. No. 6,544,556 discloses solid oral dosage forms comprising a diclofenac extended release tablet and an enterically coated proton-pump inhibitor without a separating layer between the proton pump inhibitor and, the enteric coat; these proton pump inhibitor enteric coated beads and the diclofenac tablet are contained within a capsule.
U.S. Pat. No. 6,926,907 discloses pharmaceutical compositions in unit dose form for oral administration comprising an acid inhibitor present in an amount effective to raise the gastric pH to at least 3.5 upon the administration of one or more of said unit dosage forms; and a non-steroidal anti-inflammatory drug (NSAID) in an amount effective to reduce or eliminate pain or inflammation upon administration of one or more of said unit dosage forms.
U.S. Pat. No. 6,869,615 discloses solid oral dosage forms comprising a population of substrates comprising a proton-pump inhibitor; an enteric coating layer coated over said substrates; and an NSAID coating layer coated over said enteric-coated substrates.
U.S. Patent Application No. 20050249806 discloses pharmaceutical compositions comprising a therapeutically effective amount of at least one acid labile proton pump inhibitor; at least one buffering agent in an amount sufficient to increase gastric fluid pH to a pH that prevents acid degradation of at least some of the proton pump inhibitor in the gastric fluid; and a therapeutically effective amount of at least one nonsteroidal anti-inflammatory drug.
U.S. Patent Application No. 20050163847 discloses solid oral dosage forms comprising a first portion comprising a therapeutically effective amount of an NSAID; and a coating comprising a therapeutically effective amount of an anti ulcerative compound; said coating at least partially surrounding said first NSAID portion.
However, despite the therapeutic benefits of NSAIDs, their use is often limited by an increased risk of gastrointestinal side effects, in particular upper gastrointestinal side effects such as peptic ulceration and dyspeptic symptoms. It is also well known that NSAIDs have the potential to cause gastrointestinal (GI) bleeding through a variety of mechanisms related to their topical and systemic effects. The GI bleeding may depend on the length of the treatment and on the particular drug. This problem is important in cases where the therapy must be continued for a long period of time.
Therefore, there exists a need in the art for a combination formulation, which includes an NSAID, analgesic-antipyretic with proton pump inhibitor to reduce the occurrence of gastro-intestinal side effects associated with NSAID treatment.